The long-term objective of this project is to develop protein arrays for high-throughput screening of ligands for nuclear hormone receptors. In this phase I grant, a limited nuclear hormone receptor array will be developed to determine the feasibility of these arrays and to compare the ligand binding characteristics of nuclear hormone receptors on these arrays with endogenous receptors. In this stage, we will focus on radiolabeled ligands as these have been well documented. In phase II, the nuclear hormone receptor array will be extended to include all 48 members of the nuclear hormone receptor superfamily and we will expand to the use of fluorescently labeled ligands which would bring this technology in compatability with high throughput DNA array readers that are already commercially available. These arrays can then be used to determine specificity/cross-reactivity (and potential side-effects) of a particular ligand against all receptors in this family. The ligand-based array will be expanded in phase II to test the use of these arrays for screening novel compounds as potential ligands for a nuclear hormone receptor. This research is highly relevant to public health as drugs that target nuclear hormone receptors comprise 10-15% of the $400 billion dollar global pharmaceutical market. Although these drugs are effective, many have undesirable side-effects and because of this the pharmaceutical industry is continuously developing new drugs that specifically target one member of the nuclear hormone receptor superfamily and are devoid of some of the undesirable side-effects. This research will provide a rapid method of screening new compounds for nuclear hormone receptor binding and determining specificity of that binding. [unreadable] [unreadable] [unreadable]